Physical Sciences Inc. (PSI) has successfully completed a Phase I program demonstrating the feasibility of integrating adaptive optics (AO) into a line scanning laser ophthalmoscope (LSLO). The bench-top AO-LSLO instrument significantly reduces the size, complexity, and cost of research AOSLOs, for the purpose of moving adaptive optics imaging more quickly into routine clinical use. The AO-LSLO produces high resolution retinal images with only one moving part and a significantly reduced instrument footprint and number of optical components. The AO-LSLO has a moderate field of view (5.5 deg), which allows montages of the macula or other targets to be obtained more quickly and efficiently. In a preliminary human subjects investigation, photoreceptors could be resolved and counted to within ~0.5 mm of the fovea. Photoreceptor counts matched closely to previously reported histology. The capillaries surrounding the foveal avascular zone could be resolved, as well as cells flowing within them. Individual nerve fiber bundles could be resolved, especially near the optic nerve head, as well as other structures such as the lamina cribrosa. In addition to instrument design, fabrication, and testing, software algorithms were developed for automated image registration, cone counting, and montage stitching. In collaboration with ophthalmologists at Duke University Eye Center, we propose to continue instrument development and full clinical testing in Phase II. The AO-LSLO instrument will be refined and enhanced for clinical operation, including re-design of the optical layout for a smaller footprint, opto- mechanical design of a clinical package, modification of scanning hardware for automatic montaging, and upgrade of some components for improved performance. In addition, we will explore further reduction of hardware complexity with the implementation of wave front sensorless algorithms. The pilot clinical study at Duke will be conducted in three stages. The first stage will accomplish preliminary testing in a clinical environment. The second stage will include a repeatability study, image several different retinal diseases (Stargardt's, retinitis pigmentosa, etc.), and compare the AO-LSLO to other imaging modalities currently in routine clinical use. The third stage will explore the instrument's capabilities to image photoreceptors in dry age-related macular degeneration (AMD) at the margin of sites of geographic atrophy (GA) and in diabetic macula edema at sites of previous laser treatment. In particular we will characterize and quantify photoreceptor loss across these sites of disease or laser treatment and other inner retinal components. This study will determine if the AO-LSLO provides complementary information not currently available from other imaging modes. If successful, the Phase II program and subsequent Phase III commercial development will provide clinicians with high-resolution, high performance adaptive optics imaging at a cost comparable to other retinal imagers to help guide therapies and improve patient outcomes. PUBLIC HEALTH RELEVANCE: By making high-resolution ocular access more widespread, the proposed AO-LSLO instrument will bring adaptive optics technology into use by a greater number of clinicians and scientists. These researchers will, in turn, use this tool to increase our understanding of vision and its disruption by disease and to measure tissue effects of new drugs and therapies.